Polyfunctional Cytomegalovirus‐Specific CD4+ and pp65 CD8+ T Cells Protect Against High‐Level Replication After Liver Transplantation

To determine whether polyfunctional CD4+ T‐cell responses coupled with CD8+ T‐cell responses against human cytomegalovirus (HCMV) are key to the control of HCMV replication we prospectively analyzed 29 liver transplant recipients for CD4+ T‐cell responses against soluble HCMV antigen, pp65 and IE1 proteins, CD8+ T‐cell responses against pp65 and IE1 proteins and a range of T helper (Th) 1 and Th2 cytokines. Eleven patients (38%) developed HCMV DNAemia at a median of 21 days post‐liver transplantation (range 17–31 days). There was a significantly lower frequency and absolute number of total HCMV CD4+ T cells producing IFNγ, IFNγ+IL2 and IL2 and pp65‐CD8+ T cells producing IFNγ in patients with DNAemia. The quantities of Th1 and Th2 cytokines present during the first 20 days posttransplant were not predictive of DNAemia. Cut‐off levels during the first 20 days posttransplant of 0.1% of lysate stimulated CD4+ T cells producing IL2, and pp65‐CD8+ T cells producing IFNγ above 0.4% had positive and negative predictive values for DNAemia of 54% and 100% and 50% and 92%, respectively. Measuring polyfunctional CD4+ T cells against HCMV early posttransplant may allow targeted intervention to minimize the occurrence and acute and long‐term consequences of HCMV replication.